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New Insights to Nuclear Receptor Gene Regulation from Analysis of their Response Elements in Target Genes

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Nuclear Receptors

Part of the book series: Proteins and Cell Regulation ((PROR,volume 8))

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Abstract

Nuclear receptor (NR) target genes have key roles in cellular metabolism, cellular growth and differentiation and in controlling inflammation. Many NR target genes are also involved in dysregulated pathways that can lead to common human diseases, such as type 2 diabetes, atherosclerosis, Alzheimer’s disease and cancer. On the genomic level these pathways converge on regulatory modules, some of which contain co-localizing NR binding sites, so-called response elements (REs). Recent advances in genomic techniques combined with computational analysis of binding modules are discussed in this chapter, primarily at the example of the NRs vitamin D receptor (VDR or NR1I1) and peroxisome proliferator-activated receptors (PPARα or NR1C1, PPARβ/δ or NR1C2 and PPARγ or NR1C3).

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References

  1. Sperling, S. (2007). Transcriptional regulation at a glance. BMC Bioinformatics 8(Suppl 6), S2.

    Article  PubMed  Google Scholar 

  2. Carlberg, C. and Dunlop, T. W. (2006). The impact of chromatin organization of vitamin D target genes. Anticancer Res 26, 2637–2645.

    CAS  PubMed  Google Scholar 

  3. Carlberg, C., Dunlop, T. W., Saramäki, A., Sinkkonen, L., Matilainen, M., and Väisänen, S. (2007). Controlling the chromatin organization of vitamin D target genes by multiple vitamin D receptor binding sites. J Steroid Biochem Mol Biol 103, 338–343.

    Article  CAS  PubMed  Google Scholar 

  4. Jones, S. J. (2006). Prediction of genomic functional elements. Annu Rev Genomics Hum Genet 7, 315–338.

    Article  CAS  PubMed  Google Scholar 

  5. Demeret, C., Vassetzky, Y., and Mechali, M. (2001). Chromatin remodelling and DNA replication: from nucleosomes to loop domains. Oncogene 20, 3086–3093.

    Article  CAS  PubMed  Google Scholar 

  6. Valouev, A., Johnson, D. S., Sundquist, A., Medina, C., Anton, E., Batzoglou, S., Myers, R. M., and Sidow, A. (2008). Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data. Nat Methods 5, 829–834.

    Article  CAS  PubMed  Google Scholar 

  7. Chawla, A., Repa, J. J., Evans, R. M., and Mangelsdorf, D. J. (2001). Nuclear receptors and lipid physiology: opening the X-files. Science 294, 1866–1870.

    Article  CAS  PubMed  Google Scholar 

  8. Nuclear-Receptor-Committee (1999). A unified nomenclature system for the nuclear receptor superfamily. Cell 97, 161–163.

    Article  Google Scholar 

  9. Maglich, J. M., Sluder, A., Guan, X., Shi, Y., McKee, D. D., Carrick, K., Kamdar, K., Willson, T. M., and Moore, J. T. (2001). Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes. Genome Biol 2, R29.

    Article  Google Scholar 

  10. Bertrand, S., Brunet, F. G., Escriva, H., Parmentier, G., Laudet, V., and Robinson-Rechavi, M. (2004). Evolutionary genomics of nuclear receptors: from twenty-five ancestral genes to derived endocrine systems. Mol Biol Evol 21, 1923–1937.

    Article  CAS  PubMed  Google Scholar 

  11. Bookout, A. L., Jeong, Y., Downes, M., Yu, R. T., Evans, R. M., and Mangelsdorf, D. J. (2006). Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 126, 789–799.

    Article  CAS  PubMed  Google Scholar 

  12. Mohan, R. and Heyman, R. A. (2003). Orphan nuclear receptor modulators. Curr Top Med Chem 3, 1637–1647.

    Article  CAS  PubMed  Google Scholar 

  13. Nettles, K. W. and Greene, G. L. (2005). Ligand control of coregulator recruitment to nuclear receptors. Annu Rev Physiol 67, 309–333.

    Article  CAS  PubMed  Google Scholar 

  14. Giguere, V. (1999). Orphan nuclear receptors: from gene to function. Endocr Rev 20, 689–725.

    Article  CAS  PubMed  Google Scholar 

  15. Rochel, N., Wurtz, J. M., Mitschler, A., Klaholz, B., and Moras, D. (2000). Crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell 5, 173–179.

    Article  CAS  PubMed  Google Scholar 

  16. Moras, D. and Gronemeyer, H. (1998). The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol 10, 384–391.

    Article  CAS  PubMed  Google Scholar 

  17. Kersten, S., Desvergne, B., and Wahli, W. (2000). Roles of PPARs in health and disease. Nature 405, 421–424.

    Article  CAS  PubMed  Google Scholar 

  18. Aranda, A. and Pascual, A. (2001). Nuclear hormone receptors and gene expression. Physiol Rev 81, 1269–1304.

    CAS  PubMed  Google Scholar 

  19. Burke, L. J. and Baniahmad, A. (2000). Co-repressors 2000. FASEB J 14, 1876–1888.

    Article  CAS  PubMed  Google Scholar 

  20. Polly, P., Herdick, M., Moehren, U., Baniahmad, A., Heinzel, T., and Carlberg, C. (2000). VDR-Alien: a novel, DNA-selective vitamin D3 receptor-corepressor partnership. FASEB J 14, 1455–1463.

    Article  CAS  PubMed  Google Scholar 

  21. Privalsky, M. L. (2004). The role of corepressors in transcriptional regulation by nuclear hormone receptors. Annu Rev Physiol 66, 315–360.

    Article  CAS  PubMed  Google Scholar 

  22. Leo, C. and Chen, J. D. (2000). The SRC family of nuclear receptor coactivators. Gene 245, 1–11.

    Article  CAS  PubMed  Google Scholar 

  23. Castillo, A. I., Jimenez-Lara, A. M., Tolon, R. M., and Aranda, A. (1999). Synergistic activation of the prolactin promoter by vitamin D receptor and GHF-1: role of coactivators, CREB-binding protein and steroid hormone receptor coactivator-1 (SRC-1). Mol Endocrinol 13, 1141–1154.

    Article  CAS  PubMed  Google Scholar 

  24. Rachez, C., Suldan, Z., Ward, J., Chang, C. -P., Burakov, D., Erdjument-Bromage, H., Tempst, P., and Freedman, L. P. (1998). A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances transactivation in a cell-free system. Genes Dev 12, 1787–1800.

    Article  CAS  PubMed  Google Scholar 

  25. Rachez, C., Lemon, B. D., Suldan, Z., Bromleigh, V., Gamble, M., Näär, A. M., Erdjument-Bromage, H., Tempst, P., and Freedman, L. P. (1999). Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398, 824–828.

    Article  CAS  PubMed  Google Scholar 

  26. Khanim, F. L., Gommersall, L. M., Wood, V. H., Smith, K. L., Montalvo, L., O’Neill, L. P., Xu, Y., Peehl, D. M., Stewart, P. M., Turner, B. M. et al. (2004). Altered SMRT levels disrupt vitamin D3 receptor signalling in prostate cancer cells. Oncogene 23, 6712–6725.

    Article  CAS  PubMed  Google Scholar 

  27. Malinen, M., Saramäki, A., Ropponen, A., Degenhardt, T., Väisänen, S., and Carlberg, C. (2008). Distinct HDACs regulate the transcriptional response of human cyclin-dependent kinase inhibitor genes to Trichostatin A and 1a,25-dihydroxyvitamin D3. Nucleic Acids Res 36, 121–132.

    Article  CAS  PubMed  Google Scholar 

  28. Metivier, R., Penot, G., Hubner, M. R., Reid, G., Brand, H., Kos, M., and Gannon, F. (2003). Estrogen receptor a directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115, 751–763.

    Article  CAS  PubMed  Google Scholar 

  29. Kim, S., Shevde, N. K., and Pike, J. W. (2005). 1,25-Dihydroxyvitamin D3 stimulates cyclic vitamin D receptor/retinoid X receptor DNA-binding, co-activator recruitment, and histone acetylation in intact osteoblasts. J Bone Miner Res 20, 305–317.

    Article  CAS  PubMed  Google Scholar 

  30. Saramäki, A., Diermeier, S., Kellner, R., Laitinen, H., Väisänen, S., and Carlberg, C. (2009). Cyclical chromatin looping and transcription factor association on the regulatory regions of the p21 (CDKN1A) gene in response to 1a,25-dihydroxyvitamin D3. J Biol Chem 284, 8073–8082.

    Article  PubMed  Google Scholar 

  31. Degenhardt, T., Rybakova, K. N., Tomaszweska, A., Mone, M. J., Westerhoff, H. V., Bruggeman, F. J., and Carlberg, C. (2009). Population-level transcription cycles derive from stochastic timing of single-cell transcription. Cell 138(3), 489–501.

    Article  CAS  PubMed  Google Scholar 

  32. Kang, Z., Pirskanen, A., Jänne, O. A., and Palvimo, J. J. (2002). Involvement of proteasome in the dynamic assembly of the androgen receptor transcription complex. J Biol Chem 277, 48366–48371.

    Article  CAS  PubMed  Google Scholar 

  33. Karpova, T. S., Kim, M. J., Spriet, C., Nalley, K., Stasevich, T. J., Kherrouche, Z., Heliot, L., and McNally, J. G. (2008). Concurrent fast and slow cycling of a transcriptional activator at an endogenous promoter. Science 319, 466–469.

    Article  CAS  PubMed  Google Scholar 

  34. Väisänen, S., Dunlop, T. W., Sinkkonen, L., Frank, C., and Carlberg, C. (2005). Spatio-temporal activation of chromatin on the human CYP24 gene promoter in the presence of 1a,25-dihydroxyvitamin D3. J Mol Biol 350, 65–77.

    Article  PubMed  Google Scholar 

  35. Sharma, D. and Fondell, J. D. (2002). Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo. Proc Natl Acad Sci U S A 99, 7934–7939.

    Article  CAS  PubMed  Google Scholar 

  36. Jenuwein, T. and Allis, C. D. (2001). Translating the histone code. Science 293, 1074–1080.

    Article  CAS  PubMed  Google Scholar 

  37. Berger, S. L. (2007). The complex language of chromatin regulation during transcription. Nature 447, 407–412.

    Article  CAS  PubMed  Google Scholar 

  38. Perissi, V. and Rosenfeld, M. G. (2005). Controlling nuclear receptors: the circular logic of cofactor cycles. Nat Rev Mol Cell Biol 6, 542–554.

    Article  CAS  PubMed  Google Scholar 

  39. Acevedo, M. L. and Kraus, W. L. (2004). Transcriptional activation by nuclear receptors. Essays Biochem 40, 73–88.

    CAS  PubMed  Google Scholar 

  40. Luisi, B. F., Xu, W. X., Otwinowski, Z., Freedman, L. P., Yamamoto, K. R., and Sigler, P. B. (1991). Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352, 497–505.

    Article  CAS  PubMed  Google Scholar 

  41. Khorasanizadeh, S. and Rastinejad, F. (2001). Nuclear-receptor interactions on DNA-response element. Trends Biochem Sci 26, 384–390.

    Article  CAS  PubMed  Google Scholar 

  42. Carlberg, C. (1999). Lipid soluble vitamins in gene regulation. Biofactors 10, 91–97.

    Article  CAS  PubMed  Google Scholar 

  43. Carlberg, C., Bendik, I., Wyss, A., Meier, E., Sturzenbecker, L. J., Grippo, J. F., and Hunziker, W. (1993). Two nuclear signalling pathways for vitamin D. Nature 361, 657–660.

    Article  CAS  PubMed  Google Scholar 

  44. MacDonald, P. N., Dowd, D. R., Nakajima, S., Galligan, M. A., Reeder, M. C., Haussler, C. A., Ozato, K., and Haussler, M. R. (1993). Retinoid X receptors stimulate and 9-cis retinoic acid inhibits 1,25-dihydroxyvitamin D3-activated expression of the rat osteocalcin gene. Mol Cell Biol 13, 5907–5917.

    CAS  PubMed  Google Scholar 

  45. Schräder, M., Müller, K. M., Nayeri, S., Kahlen, J. P., and Carlberg, C. (1994). VDR-T3R receptor heterodimer polarity directs ligand sensitivity of transactivation. Nature 370, 382–386.

    Article  PubMed  Google Scholar 

  46. Schräder, M., Nayeri, S., Kahlen, J. P., Müller, K. M., and Carlberg, C. (1995). Natural vitamin D3 response elements formed by inverted palindromes: polarity-directed ligand sensitivity of vitamin D3 receptor-retinoid X receptor heterodimer-mediated transactivation. Mol Cell Biol 15, 1154–1161.

    PubMed  Google Scholar 

  47. Carlberg, C. (1995). Mechanisms of nuclear signalling by vitamin D3. Interplay with retinoid and thyroid hormone signalling. Eur J Biochem 231, 517–527.

    Article  CAS  PubMed  Google Scholar 

  48. Toell, A., Polly, P., and Carlberg, C. (2000). All natural DR3-type vitamin D response elements show a similar functionality in vitro. Biochem J 352, 301–309.

    Article  CAS  PubMed  Google Scholar 

  49. Rhodes, S. J., Chen, R., DiMattia, G. E., Scully, K. M., Kalla, K. A., Lin, S. -C., Yu, V. C., and Rosenfeld, M. G. (1993). A tissue-specific enhancer confers Pit-1-dependent morphogen inducibility and autoregulation on the pit-1 gene. Genes Dev 7, 913–932.

    Article  CAS  PubMed  Google Scholar 

  50. Mangelsdorf, D. J. and Evans, R. M. (1995). The RXR heterodimers and orphan receptors. Cell 83, 841–850.

    Article  CAS  PubMed  Google Scholar 

  51. Quack, M. and Carlberg, C. (2000). Ligand-triggered stabilization of vitamin D receptor/retinoid X receptor heterodimer conformations on DR4-type response elements. J Mol Biol 296, 743–756.

    Article  CAS  PubMed  Google Scholar 

  52. Turunen, M. M., Dunlop, T. W., Carlberg, C., and Väisänen, S. (2007). Selective use of multiple vitamin D response elements underlies the 1a,25-dihydroxyvitamin D3-mediated negative regulation of the human CYP27B1 gene. Nucleic Acids Res 35, 2734–2747.

    Article  CAS  PubMed  Google Scholar 

  53. Sinkkonen, L., Malinen, M., Saavalainen, K., Väisänen, S., and Carlberg, C. (2005). Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions in its promoter. Nucleic Acids Res 33, 2440–2451.

    Article  CAS  PubMed  Google Scholar 

  54. Saramäki, A., Banwell, C. M., Campbell, M. J., and Carlberg, C. (2006). Regulation of the human p21(waf1/cip1) gene promoter via multiple binding sites for p53 and the vitamin D3 receptor. Nucleic Acids Res 34, 543–554.

    Article  PubMed  Google Scholar 

  55. Matilainen, M., Malinen, M., Saavalainen, K., and Carlberg, C. (2005). Regulation of multiple insulin-like growth factor binding protein genes by 1a,25-dihydroxyvitamin D3. Nucleic Acids Res 33, 5521–5532.

    Article  CAS  PubMed  Google Scholar 

  56. Bulger, M. and Groudine, M. (1999). Looping versus linking: toward a model for long-distance gene activation. Genes Dev 13, 2465–2477.

    Article  CAS  PubMed  Google Scholar 

  57. Xie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., and Kellis, M. (2005). Systematic discovery of regulatory motifs in human promoters and 3’ UTRs by comparison of several mammals. Nature 434, 338–345.

    Article  CAS  PubMed  Google Scholar 

  58. Seuter, S., Väisänen, S., Radmark, O., Carlberg, C., and Steinhilber, D. (2007). Functional characterization of vitamin D responding regions in the human 5-lipoxygenase gene. Biochim Biophys Acta 1771, 864–872.

    CAS  PubMed  Google Scholar 

  59. Klan, N., Seuter, S., Schnur, N., Jung, M., and Steinhilber, D. (2003). Trichostatin A and structurally related histone deacetylase inhibitors induce 5-lipoxygenase promoter activity. Biol Chem 384, 777–785.

    Article  CAS  PubMed  Google Scholar 

  60. Sorg, B. L., Klan, N., Seuter, S., Dishart, D., Radmark, O., Habenicht, A., Carlberg, C., Werz, O., and Steinhilber, D. (2006). Analysis of the 5-lipoxygenase promoter and characterization of a vitamin D receptor binding site. Biochim Biophys Acta 1761, 686–697.

    CAS  PubMed  Google Scholar 

  61. Ogata, K., Sato, K., and Tahirov, T. H. (2003). Eukaryotic transcriptional regulatory complexes: cooperativity from near and afar. Curr Opin Struct Biol 13, 40–48.

    Article  CAS  PubMed  Google Scholar 

  62. Krishnan, A. V., Shinghal, R., Raghavachari, N., Brooks, J. D., Peehl, D. M., and Feldman, D. (2004). Analysis of vitamin D-regulated gene expression in LNCaP human prostate cancer cells using cDNA microarrays. Prostate 59, 243–251.

    Article  CAS  PubMed  Google Scholar 

  63. Zella, L. A., Kim, S., Shevde, N. K., and Pike, J. W. (2006). Enhancers located within two introns of the vitamin D receptor gene mediate transcriptional autoregulation by 1,25-dihydroxyvitamin D3. Mol Endocrinol 20, 1231–1247.

    Article  CAS  PubMed  Google Scholar 

  64. Meyer, M. B., Watanuki, M., Kim, S., Shevde, N. K., and Pike, J. W. (2006). The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells. Mol Endocrinol 20, 1447–1461.

    Article  CAS  PubMed  Google Scholar 

  65. Fretz, J. A., Zella, L. A., Kim, S., Shevde, N. K., and Pike, J. W. (2007). 1,25-dihydroxyvitamin D3 induces expression of the Wnt signaling co-regulator LRP5 via regulatory elements located significantly downstream of the gene’s transcriptional start site. J Steroid Biochem Mol Biol 103, 440–445.

    Article  CAS  PubMed  Google Scholar 

  66. Kim, S., Yamazaki, M., Zella, L. A., Shevde, N. K., and Pike, J. W. (2006). Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. Mol Cell Biol 26, 6469–6486.

    Article  CAS  PubMed  Google Scholar 

  67. Carroll, J. S., Meyer, C. A., Song, J., Li, W., Geistlinger, T. R., Eeckhoute, J., Brodsky, A. S., Keeton, E. K., Fertuck, K. C., Hall, G. F. et al. (2006). Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38, 1289–1297.

    Article  CAS  PubMed  Google Scholar 

  68. Cawley, S., Bekiranov, S., Ng, H. H., Kapranov, P., Sekinger, E. A., Kampa, D., Piccolboni, A., Sementchenko, V., Cheng, J., Williams, A. J. et al. (2004). Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116, 499–509.

    Article  CAS  PubMed  Google Scholar 

  69. Kwon, Y. S., Garcia-Bassets, I., Hutt, K. R., Cheng, C. S., Jin, M., Liu, D., Benner, C., Wang, D., Ye, Z., Bibikova, M. et al. (2007). Sensitive ChIP-DSL technology reveals an extensive estrogen receptor alpha-binding program on human gene promoters. Proc Natl Acad Sci U S A 104, 4852–4857.

    Article  CAS  PubMed  Google Scholar 

  70. ENCODE-Consortium (2004). The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306, 636–640.

    Article  Google Scholar 

  71. Rada-Iglesias, A., Wallerman, O., Koch, C., Ameur, A., Enroth, S., Clelland, G., Wester, K., Wilcox, S., Dovey, O. M., Ellis, P. D. et al. (2005). Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays. Hum Mol Genet 14, 3435–3447.

    Article  CAS  PubMed  Google Scholar 

  72. Nielsen, R., Pedersen, T. A., Hagenbeek, D., Moulos, P., Siersbaek, R., Megens, E., Denissov, S., Borgesen, M., Francoijs, K. J., Mandrup, S. et al. (2008). Genome-wide profiling of PPARg:RXR and RNA polymerase II occupancy reveals temporal activation of distinct metabolic pathways and changes in RXR dimer composition during adipogenesis. Genes Dev 22, 2953–2967.

    Article  CAS  PubMed  Google Scholar 

  73. Lefterova, M. I., Zhang, Y., Steger, D. J., Schupp, M., Schug, J., Cristancho, A., Feng, D., Zhuo, D., Stoeckert, C. J., Jr., Liu, X. S. et al. (2008). PPARg and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev 22, 2941–2952.

    Article  CAS  PubMed  Google Scholar 

  74. Hancock, R. (2000). A new look at the nuclear matrix. Chromosoma 109, 219–225.

    Article  CAS  PubMed  Google Scholar 

  75. Sierra, J., Villagra, A., Paredes, R., Cruzat, F., Gutierrez, S., Javed, A., Arriagada, G., Olate, J., Imschenetzky, M., Van Wijnen, A. J. et al. (2003). Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity. Mol Cell Biol 23, 3339–3351.

    Article  CAS  PubMed  Google Scholar 

  76. Cook, P. R. (1999). The organization of replication and transcription. Science 284, 1790–1795.

    Article  CAS  PubMed  Google Scholar 

  77. Olave, I. A., Reck-Peterson, S. L., and Crabtree, G. R. (2002). Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem 71, 755–781.

    Article  CAS  PubMed  Google Scholar 

  78. Stein, G. S., Zaidi, S. K., Braastad, C. D., Montecino, M., van Wijnen, A. J., Choi, J. Y., Stein, J. L., Lian, J. B., and Javed, A. (2003). Functional architecture of the nucleus: organizing the regulatory machinery for gene expression, replication and repair. Trends Cell Biol 13, 584–592.

    Article  CAS  PubMed  Google Scholar 

  79. Narlikar, G. J., Fan, H. Y., and Kingston, R. E. (2002). Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475–487.

    Article  CAS  PubMed  Google Scholar 

  80. White, J. H. (2004). Profiling 1,25-dihydroxyvitamin D3-regulated gene expression by microarray analysis. J Steroid Biochem Mol Biol 89–90, 239–244.

    Article  PubMed  Google Scholar 

  81. Pascual, G. and Glass, C. K. (2006). Nuclear receptors versus inflammation: mechanisms of transrepression. Trends Endocrinol Metab 17, 321–327.

    Article  CAS  PubMed  Google Scholar 

  82. Murayama, A., Kim, M. S., Yanagisawa, J., Takeyama, K., and Kato, S. (2004). Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching. EMBO J 23, 1598–1608.

    Article  CAS  PubMed  Google Scholar 

  83. Towers, T. L. and Freedman, L. P. (1998). Granulocyte-macrophage colony-stimulating factor gene transcription is directly repressed by the vitamin D3 receptor: implications for allosteric influences on nuclear receptor structure and function by a DNA element. J Biol Chem 273, 10338–10348.

    Article  CAS  PubMed  Google Scholar 

  84. Towers, T. L., Staeva, T. P., and Freedman, L. P. (1999). A two-hit mechanism for vitamin D3-dediates transcriptional repression of the granulocyte-macrophage colony-stimulating factor gene: vitamin D receptor completes for DNA binding with NFAT1 and stabilizes c-Jun. Mol Cell Biol 19, 4191–4199.

    CAS  PubMed  Google Scholar 

  85. Polly, P., Carlberg, C., Eisman, J. A., and Morrison, N. A. (1997). 1a,25-dihydroxyvitamin D3 receptor as a mediator of transrepression of retinoid signaling. J Cell Biochem 67, 287–296.

    Article  CAS  PubMed  Google Scholar 

  86. Heinäniemi, M., Uski, J. O., Degenhardt, T., and Carlberg, C. (2007). Meta-analysis of primary target genes of peroxisome proliferator-activated receptors. Genome Biol 8, R147.

    Article  PubMed  Google Scholar 

  87. Wang, T. T., Tavera-Mendoza, L. E., Laperriere, D., Libby, E., MacLeod, N. B., Nagai, Y., Bourdeau, V., Konstorum, A., Lallemant, B., Zhang, R. et al. (2005). Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 19, 2685–2695.

    Article  CAS  PubMed  Google Scholar 

  88. Mader, S., Leroy, P., Chen, J. -Y., and Chambon, P. (1993). Multiple parameters control the selectivity of nuclear receptors for their response elements. J Biol Chem 268, 591–600.

    CAS  PubMed  Google Scholar 

  89. Schräder, M., Müller, K. M., Becker-André, M., and Carlberg, C. (1994). Response element selectivity for heterodimerization of vitamin D receptors with retinoic acid and retinoid X receptors. J Mol Endocrinol 12, 327–339.

    Article  PubMed  Google Scholar 

  90. Schräder, M., Müller, K. M., and Carlberg, C. (1994). Specificity and flexibility of vitamin D signaling. Modulation of the activation of natural vitamin D response elements by thyroid hormone. J Biol Chem 269, 5501–5504.

    PubMed  Google Scholar 

  91. Schräder, M., Becker-Andre, M., and Carlberg, C. (1994). Thyroid hormone receptor functions as monomeric ligand-induced transcription factor on octameric half-sites. Consequences also for dimerization. J Biol Chem 269, 6444–6449.

    PubMed  Google Scholar 

  92. Carlberg, C. and Polly, P. (1998). Gene regulation by vitamin D3. Crit Rev Eukaryot Gene Expr 8, 19–42.

    CAS  PubMed  Google Scholar 

  93. Barski, A., Cuddapah, S., Cui, K., Roh, T. Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., and Zhao, K. (2007). High-resolution profiling of histone methylations in the human genome. Cell 129, 823–837.

    Article  CAS  PubMed  Google Scholar 

  94. Matys, V., Fricke, E., Geffers, R., Gossling, E., Haubrock, M., Hehl, R., Hornischer, K., Karas, D., Kel, A. E., Kel-Margoulis, O. V. et al. (2003). TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 31, 374–378.

    Article  CAS  PubMed  Google Scholar 

  95. Lemay, D. G. and Hwang, D. H. (2006). Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics. J Lipid Res 47, 1583–1587.

    Article  CAS  PubMed  Google Scholar 

  96. Wasserman, W. W. and Sandelin, A. (2004). Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet 5, 276–287.

    Article  CAS  PubMed  Google Scholar 

  97. Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., and Fraenkel, E. (2007). Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39, 730–732.

    Article  CAS  PubMed  Google Scholar 

  98. Burns, J. L., Jackson, D. A., and Hassan, A. B. (2001). A view through the clouds of imprinting. FASEB J 15, 1694–1703.

    Article  CAS  PubMed  Google Scholar 

  99. Degenhardt, T., Matilainen, M., Herzig, K. H., Dunlop, T. W., and Carlberg, C. (2006). The insulin-like growth factor-binding protein 1 gene is a primary target of peroxisome proliferator-activated receptors. J Biol Chem 281, 39607–39619.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Life Sciences Research Unit, University of Luxembourg, L-1511, Luxembourg City, Luxembourg

    Carsten Carlberg

  2. Department of Biosciences, University of Kuopio, FIN-70211, Kuopio, Finland

    Carsten Carlberg

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  1. Carsten Carlberg
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  1. School of Biosciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom

    Chris M. Bunce

  2. Dept. Pharmacology & Therapeutics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, 14263, U.S.A.

    Moray J. Campbell

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Carlberg, C. (2010). New Insights to Nuclear Receptor Gene Regulation from Analysis of their Response Elements in Target Genes. In: Bunce, C., Campbell, M. (eds) Nuclear Receptors. Proteins and Cell Regulation, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3303-1_17

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